Preoperative Oestrogen in Postmenopausal Women With Pelvic Organ Prolapse

Pelvic Organ Prolapse Clinical Trial

Official title:

Preoperative Locally Applied Oestrogen in Postmenopausal Women With Pelvic Organ Prolapse: Changes in Subjective and Objective Outcome - a Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03779633
• Other study ID #: EstrogenPOP
• Status: Completed
• Phase: Phase 4
• Start date: February 2, 2017
• Est. completion date: August 27, 2020

Study information

• Verified date: November 2020
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Introduction With increasing age the incidence of pelvic organ prolapse (POP) rises and will increase substantially in the future according to forecasting studies. It is possible that oestrogens, alone or in combination with other forms of therapy, may assist in the management of POP by increasing collagen synthesis and thereby improving the strength of the weakened vaginal epithelium. Yet, studies investigating the effect of topical oestrogen and its impact on POP associated symptoms, both self-reported improvement and observations of objective improvement, are lacking.

Objective To evaluate the subjective efficacy concerning prolapse associated complaints measured by the German pelvic floor questionnaire (domain POP: POP-score) after preoperative use of local oestrogen compared to preoperative placebo treatment in postmenopausal women with symptomatic pelvic organ prolapse. Further variables of interest are POP-score after 3 months, differences regarding the objective prolapse quantification system (POP-Q), surgical outcome and tissue operability assessed by the surgeon.

Methods In this prospective, randomized, double-blind, placebo-controlled, multicenter study the investigators aim to include 120 postmenopausal women with symptomatic pelvic organ prolapse and indicated operative procedure. An analysis of covariance will be computed with the depending variable POP-score after 6 weeks and the independent variables group (verum versus placebo) and Pop-Score at baseline.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: August 27, 2020
• Est. primary completion date: August 27, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Postmenopausal women

• Able to read, understand and sign informed consent

• Able to apply a vaginal cream

• Symptomatic pelvic organ prolapse with planned and indicated prolapse surgical repair

Exclusion Criteria:

• Suspicion or history of breast cancer or other oestrogen responsive malignancies (endometrial cancer)

• unexplained abnormal vaginal bleeding

• history of deep vein thrombosis

• inherited or acquired blood clotting disorders (eg, APC resistance, Antithrombin III deficiency)

• transient ischaemic attack, myo- cardial infarction or ischaemic heart disease

• Hypersensitivity to oestrogen

• Unable to read and sign informed consent

Related Conditions & MeSH terms

• Pelvic Organ Prolapse
• Prolapse

Intervention

Drug:
• Linoladiol Estradiol
Linoladiol Estradiol Initial dose (week 1): 1 application (2g Linoladiol = 0.2mg Estradiol) every day for the first week Maintenance dose 1 (week 2) : 1 application (2g Linoladiol = 0.2mg Estradiol) every 48 hours the following week. Maintenance dose 2 (week 3-6): 1 application (2g Linoladiol = 0.2mg Estradiol) twice per week the following 4 weeks. Route of administration: intravaginally by means of a calibrated applicator before retiring at night Duration: 6 weeks

Other:
• Placebo vaginal cream
Initial dose (week 1): 1 application every day for the first week Maintenance dose 1 (week 2) : 1 application every 48 hours the following week. Maintenance dose 2 (week 3-6): 1 application twice per week the following 4 weeks. Route of administration: intravaginally by means of a calibrated applicator before retiring at night Duration: 6 weeks

Locations

Country	Name	City	State
Austria	Department of Obstetrics and Gynecology, University of Tulln	Tulln
Austria	Department of General Gynecology and Gynecologic Oncology of the Medical University Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

References & Publications (2)

Rahn DD, Good MM, Roshanravan SM, Shi H, Schaffer JI, Singh RJ, Word RA. Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab. 2014 Oct;99(10):3728-36. doi: 10.1210/jc.2014-1216. Epub 2014 Jun 20. — View Citation

Weber MA, Kleijn MH, Langendam M, Limpens J, Heineman MJ, Roovers JP. Local Oestrogen for Pelvic Floor Disorders: A Systematic Review. PLoS One. 2015 Sep 18;10(9):e0136265. doi: 10.1371/journal.pone.0136265. eCollection 2015. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	subjective prolapse associated symptoms (measured with the validated German pelvic floor questionnaire)	treatment efficacy of preoperative vaginally administered oestrogen in postmenopausal women with symptomatic pelvic organ prolapse in comparison to placebo, measured by a subjective questionnaire. 42 questions. Range 0 to 3 points for each question. Lower values represent a better outcome	change from baseline POP Score at 6 weeks after treatment
Secondary	operative time in minutes	effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo	up to 1 week postoperative
Secondary	length of stay in days	effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo	up to 1 week postoperative
Secondary	intraoperative blood loss in ml	effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo	up to 1 week postoperative
Secondary	blood circulation of the tissue (good, regular, scarce, no blood circulation)	differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation	on day of surgery
Secondary	separability of the tissue layers (good, regular, scarce, not possible)	differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation	on day of surgery
Secondary	easy separation from the bladder (yes/no)	differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation	on day of surgery
Secondary	easy opening of the Douglas cavity (Yes/no)	differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation	on day of surgery
Secondary	subjective (all domains of the pelvic floor questionnaire) outcome 3 months postoperative	possible differences regarding subjective outcome parameters between intervention and placebo-group 3 months after operation. 42 questions. Range 0 to 3 points for each question. Lower values represent a better outcome.	3 months postoperative
Secondary	objective (POP-Q score) outcome 3 months postoperative	possible differences regarding objective outcome parameters between intervention and placebo-group 3 months after operation. POP-Q Score (Score between 0 and 4). The POP- quantification system consists of six defined points of measurement (Aa, Ba, C,D,Ap,Bp) and three other landmarks (GH,TVL, PB). Each is measured in centimeters above the hymen (negative number) or below the hymen (positive number).	3 months postoperative